Soluble CCL5 derived from bone marrow-derived mesenchymal stem cells and activated by amyloid β ameliorates Alzheimer's disease in mice by recruiting bone marrow-induced microglia immune responses

Stem Cells
Jong Kil LeeJae-Sung Bae

Abstract

Microglia have the ability to eliminate amyloid β (Aβ) by a cell-specific phagocytic mechanism, and bone marrow (BM) stem cells have shown a beneficial effect through endogenous microglia activation in the brains of Alzheimer's disease (AD) mice. However, the mechanisms underlying BM-induced activation of microglia have not been resolved. Here we show that BM-derived mesenchymal stem cells (MSCs) induced the migration of microglia when exposed to Aβ in vitro. Cytokine array analysis of the BM-MSC media obtained after stimulation by Aβ further revealed elevated release of the chemoattractive factor, CCL5. We also observed that CCL5 was increased when BM-MSCs were transplanted into the brains of Aβ-deposited AD mice, but not normal mice. Interestingly, alternative activation of microglia in AD mice was associated with elevated CCL5 expression following intracerebral BM-MSC transplantation. Furthermore, by generating an AD-green fluorescent protein chimeric mouse, we ascertained that endogenous BM cells, recruited into the brain by CCL5, induced microglial activation. Additionally, we observed that neprilysin and interleukin-4 derived from the alternative microglia were associated with a reduction in Aβ deposition and memory impai...Continue Reading

References

Jun 20, 2000·Neurobiology of Aging·H AkiyamaT Wyss-Coray
Apr 4, 2003·The Journal of Biological Chemistry·Peter Devreotes, Chris Janetopoulos
Jun 3, 2004·Neurobiology of Aging·Michael R D'AndreaMarch D Ard
Apr 29, 2005·Brain : a Journal of Neurology·Yang LiuKlaus Fassbender
Jul 12, 2005·Journal of Alzheimer's Disease : JAD·Milan FialaGeorge Bernard
Jul 26, 2006·Proceedings of the National Academy of Sciences of the United States of America·Oleg ButovskyMichal Schwartz
Jan 26, 2007·Journal of Neurochemistry·Anthony LyonsMarina A Lynch
Mar 24, 2007·Rejuvenation Research·Barry E FlanaryWolfgang J Streit
May 15, 2007·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Ming ZhangMarc S Penn
Aug 7, 2007·International Review of Neurobiology·Richard M RansohoffAstrid E Cardona
Apr 9, 2008·Trends in Immunology·Nathalie DavoustSerge Nataf
Jun 3, 2008·Nature Medicine·Terrence TownRichard A Flavell
Aug 15, 2008·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Suzanne E HickmanJoseph El Khoury
Sep 17, 2008·Proceedings of the National Academy of Sciences of the United States of America·Hirokazu OhtakiDarwin J Prockop
Nov 7, 2008·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Sebastian JimenezJavier Vitorica
Feb 6, 2009·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Kate Lykke LambertsenBente Finsen
Oct 21, 2009·Neuron·V Wee Yong, Serge Rivest
Nov 21, 2009·Cytokine & Growth Factor Reviews·Lindolfo da Silva MeirellesArnold I Caplan
Apr 8, 2010·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Tomomi KiyotaTsuneya Ikezu
May 5, 2010·The Journal of Experimental Medicine·Noël C DereckiJonathan Kipnis
Feb 25, 2011·Current Alzheimer Research·K Rezai-ZadehT Town

❮ Previous
Next ❯

Citations

Apr 13, 2013·Journal of Neuroimmune Pharmacology : the Official Journal of the Society on NeuroImmune Pharmacology·Alice LaroniAntonio Uccelli
Jan 17, 2013·Stem Cells and Development·Micaela Johanna Glat, Daniel Offen
Jul 23, 2014·The Journal of Experimental Medicine·Jong Kil LeeJae-sung Bae
Mar 15, 2013·Stem Cells Translational Medicine·Virginie NeirinckxSabine Wislet-Gendebien
Aug 13, 2013·The International Journal of Neuroscience·Zhiyou CaiLiang-Jun Yan
Oct 13, 2015·Biochimica Et Biophysica Acta·Chotima Böttcher, Josef Priller
Nov 21, 2015·Neoplasia : an International Journal for Oncology Research·Anne C SolgaDavid H Gutmann
Oct 15, 2013·Immunology·Debora GiuntiNicole Kerlero de Rosbo
Aug 5, 2015·Neurology India·Chuyi HuangHuancong Zuo
Nov 12, 2014·Journal of Molecular Neuroscience : MN·Keren Nicole HamishaGadi Turgeman
Dec 28, 2016·International Journal of Molecular Sciences·Rosaliana LibroOriana Trubiani
Jan 11, 2014·American Journal of Alzheimer's Disease and Other Dementias·Gholamreza AziziAbbas Mirshafiey
Nov 29, 2015·Proceedings of the Institution of Mechanical Engineers. Part H, Journal of Engineering in Medicine·Teresa RussoLuigi Ambrosio
Jun 24, 2017·Journal of Neuroscience Research·Zhiwei ShenRenzhi Wang
Jul 10, 2019·Journal of Internal Medicine·R Loera-ValenciaB Winblad
Apr 7, 2018·Frontiers in Aging Neuroscience·Yi FangJiali Pu
Jun 30, 2015·Journal of Tissue Engineering and Regenerative Medicine·Chaitra VenugopalAnandh Dhanushkodi

❮ Previous
Next ❯

Related Concepts

Related Feeds

Alzheimer's Disease: APP

Amyloid precursor protein (APP) proteolysis is critical for the development of Alzheimer's disease, a neurodegenerative disease associated with accumulation of amyloid plaques in the brain. Here is the latest research on APP and Alzheimer's disease.

Alzheimer's Disease: Microglia

Microglia are a type of glial cell found throughout the brain and spinal cord. Microglia have been found to be associated with Alzheimer's disease development and progression. Here are the latest discoveries pertaining to Alzheimer's disease and microglia.

Alzheimer's Disease: Amyloid Beta

Alzheimer's disease is a neurodegenerative disease associated with the accumulation of amyloid plaques in the brain; these plaques are comprised of amyloid beta deposits. Here is the latest research in this field.

Allogenic & Autologous Therapies

Allogenic therapies are generated in large batches from unrelated donor tissues such as bone marrow. In contrast, autologous therapies are manufactures as a single lot from the patient being treated. Here is the latest research on allogenic and autologous therapies.